Limulus lysate, an aqueous extract of the amebocytes obtained from the blood of the horseshoe crab, Limulus polyphemus, gels when mixed with endotoxins (pyrogens) of gram-negative bacteria. The Limulus gelatin test is used as a method for detecting pyrogens in parenteral pharmaceuticals. Although the test will normally detect low levels of endotoxins, there is a borderline region in the gelatin process where the analyst must rely heavily on visual judgment. In this project nephelometry is used to measure the rate of precipitin-like formation resulting from the reaction of Limulus lysate with endotoxins from gram-negative bacteria. The nephelometric approach indicates the detection and quantitation of pyrogen from E. coli in the pg/ml level. Evaluation of the new procedure indicates the possible use of this method for the quantitation of endotoxins for diagnostic care of NIH patients.